Preoperative serum ADAM12 levels as a stromal marker for overall survival and benefit of adjuvant therapy in patients with resected pancreatic and periampullary cancer

HPB (Oxford). 2021 Dec;23(12):1886-1896. doi: 10.1016/j.hpb.2021.05.001. Epub 2021 May 19.


Background: We evaluated the stroma marker A Disintegrin And Metalloprotease 12 (ADAM12) as a preoperative prognostic and treatment-predictive marker for overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) and periampullary cancers.

Methods: Materials were derived from the prospective nationwide Dutch Pancreas Biobank (2015-2017). We included patients who underwent resection because of PDAC/periampullary cancer or non-invasive IPMN (control group) and had a preoperative serum sample available. ADAM12 levels were dichotomized using a pre-defined cut-off (316 pg/mL). Univariable and multivariable Cox regression analyses (backward selection) were performed.

Results: Median ADAM12 levels were 161 (IQR 79-352) pg/mL in 215 PDAC and periampullary adenocarcinomas. High ADAM12 levels (>316 pg/mL) predicted poor OS in the total group of pancreatic and periampullary adenocarcinomas (P = 0.04), but not after adjustment. In distal cholangiocarcinoma (n = 33), high ADAM12 levels predicted poor OS in univariable analysis (P = 0.02), but not in PDAC (P = 0.63). PDAC patients (n = 135) with high ADAM12 levels benefited from adjuvant treatment (median OS 27 vs 14 months, P = 0.02), whereas those with low levels did not (21 vs 21 months, P = 0.87).

Conclusion: High circulating ADAM12 levels, as a proxy for activated stroma, predict survival benefit from adjuvant chemotherapy in PDAC, requiring validation in future studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM12 Protein / blood*
  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / surgery
  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Carcinoma, Pancreatic Ductal* / surgery
  • Humans
  • Pancreas
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / surgery
  • Prognosis
  • Prospective Studies
  • Retrospective Studies


  • ADAM12 Protein
  • ADAM12 protein, human